tbuckley/cabot-search huggingface dataset:
External validation of biomechanical computed tomography for fracture risk classification in metastatic hormone sensitive prostate cancer.
Authors: John Kent Lin, Caleb Hearn, Emily Getzen, Qi Long, Helayne Drell, David Lee, Tony M. Keaveny, Ravishankar Jayadevappa, Kyle William Robinson, Yu-Ning Wong, Kara Noelle Maxwell, Vivek Narayan, Naomi B. Haas, Samuel U. Takvorian, Daniel Bikle, Janet M. Chiang, Amna N. Khan, Chamith S Rajapakse, Alicia K. Morgans, Ravi Bharat Parikh
Journal: Journal of Clinical Oncology (2023)

e24077 Background: For men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT), guidelines recommend dual-energy X-ray absorptiometry (DXA) screening to identify fracture risk and benefit from antiresorptive therapy. However, only 8% of men with mHSPC receive routine DXA screening. Biomechanical computed tomography (BCT) is a radiomic technique that measures bone mineral density (BMD) and bone strength from routine staging and surveillance CT scans but has not been validated in mHSPC. Methods: This retrospective cohort study included 99 patients with incident mHSPC beginning ADT (2013-2020) at one academic (n = 70) and one tertiary VA medical center (n = 29) with CT abdomen/pelvis or PET/CT imaging at baseline (within 1 year prior to ADT initiation) and follow-up (1-2 years after ADT initiation). BCT-assessed BMD T-score and femoral strength were calculated from baseline and follow-up CT scans. We evaluated the association between BCT measures and subsequent pathologic and non-pathologic fractures within 3 years following mHSPC diagnosis. Results: Among 99 patients, mean age was 68 years, 48 (48.5%) were White, and 45 (45.4%) were Black. During median follow-up of 19 months, 23 (24%) developed a pathologic and 15 (15%) a non-pathologic fracture. BCT and DXA-assessed femoral-neck BMD T-score were strongly correlated (R 2 = 0.94, N = 23). Higher BCT-assessed baseline BMD (Odds Ratio [OR] 0.5, p = 0.03) and bone strength (OR 0.57, p = 0.02) were each associated with decreased pathologic fracture (Table). Neither BMD nor bone strength were significantly associated with non-pathologic fracture. BCT identified 10 (10%) men eligible for antiresorptive therapy by established BMD, strength, or FRAX criteria at ADT initiation, 4 (40%) of whom never received it by the end of follow-up. Between baseline and follow-up, both BMD (-0.27) and bone strength (-0.34) decreased among patients who did not receive antiresorptive therapy (n = 76), with no difference in longitudinal change between ADT alone vs with androgen receptor signaling inhibitors. Conclusions: In this diverse, multicenter cohort of men with mHSPC beginning ADT, BCT BMD assessed from routine CT scans strongly correlated with DXA-assessed BMD. BCT measurements predicted subsequent pathologic fracture and identified additional men who would benefit from antiresorptive therapy. BCT may provide a practical method to assess the role for anti-resorptive therapy in patients with mHSPC. [Table: see text]
Sleep health and quality of life in African American cancer survivors: The Detroit ROCS Cohort.
Authors: Jennifer Lynn Beebe-Dimmer, Matthew R Trendowski, Julie J. Ruterbusch, Jennifer Martin, Tara Baird, Ann G. Schwartz, Safwan Badr
Journal: Journal of Clinical Oncology (2023)

10556 Background: Sleep disturbances are particularly prevalent among cancer survivors, likely attributed in part to anxiety over prognosis, treatment, and associated financial concerns. We know little about prevalence, patterns and predictors of poor sleep health in African American (AA) cancer survivors. Sleep problems may contribute in part to the observed disparities in outcomes in this high-risk population and represents a modifiable target to improve quality of life and longer-term health problems. Methods: The Detroit Research on Cancer Survivors (ROCS) study is a large cohort of AA cancer survivors diagnosed with female breast, prostate, colorectal, endometrial, lung or any other early onset cancer on or after 01/01/2013 in Metropolitan Detroit. We have enrolled 5,073 survivors into the study, each completing a baseline survey with annual follow-up to update medical history, health related quality of life (QoL), and other prognostic factors. In 2021, a supplemental sleep survey was administered to all eligible survivors. The current investigation analyzes sleep, QoL (measured using the Functional Assessment of Cancer Therapy - General (FACT-G) survey), and relevant health behavior data from 716 survivors who completed the sleep survey. Sleep health was measured using the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). Block regression was used to estimate the contribution of clustered factors to QoL. Five blocks were evaluated: sleep health, demographics, cancer characteristics, comorbidities, and health behaviors. Results: Nearly 60% of AA cancer survivors in the study reported symptoms indicative of poor sleep quality (PSQI score 6-21) with 17% reporting excessive daytime sleepiness (ESS score 11-24) and 11% reporting moderate to severe insomnia (ISI score ≥ 15). Sleep disturbances and poor quality of sleep were associated with clinically meaningful declines in QoL, where survivors with ISI scores in the clinical range reported adjusted FACT-G scores 19 points lower than those with ISI score below the clinical range (95% CI -14.7, -22.6). Sleep health accounted for the largest proportion of variability in FACT-G scores (R 2 = 0.28) and accounted for an additional 19% of the variance over and above the other 4 blocks. Finally, AA survivors reporting regular physical activity also reported better sleep quality in all 3 sleep scales (p &lt; 0.001). Conclusions: A substantial proportion of AA cancer survivors reported poor sleep quality which impacted their QoL. Understanding the determinants of sleep health in this population will lead to the development of interventions aimed at improving quality of life and downstream health consequences in AA cancer survivors.
Tarlatamab in small cell lung cancer (SCLC): Safety and efficacy analyzed by baseline brain metastasis.
Authors: Stephane Champiat, Michael J. Boyer, Ramaswamy Govindan, Luis G. Paz-Ares, Taofeek K. Owonikoko, Hossein Borghaei, Hiroki Izumi, Neeltje Steeghs, Fiona Helen Blackhall, Angelika Terbuch, Melissa Lynne Johnson, Tatsuya Yoshida, Kai He, Yuyang Zhang, Simon Jones, Xi Chen, Pablo Martinez, Horst-Dieter Hummel
Journal: Journal of Clinical Oncology (2023)

8582 Background: Tarlatamab, a BiTE molecule targeting DLL3 and CD3, is being studied in patients (pts) with extensive stage small cell lung cancer (ES-SCLC). 1 Up to 25% of pts diagnosed with SCLC have brain metastases (BM) and 50% or more will develop BM during the course of the disease. Pts with ES-SCLC and BM have poor prognosis and quality of life. We analyzed the characteristics and outcomes of pts included in the tarlatamab phase 1 study (NCT03319940) who had baseline BM vs those who did not. Methods: Pts included in the phase 1 trial had SCLC that progressed after ≥1 platinum-based regimen and received tarlatamab (0.003–100 mg IV). Pts with treated BM were eligible if local therapy was delivered ≥ 2 weeks prior to first tarlatamab dose. Results: As of 03 January 2023, 192 pts had received tarlatamab as monotherapy. Median age was 62 (range, 32–80) y; 188 pts (98%) had ECOG PS 0–1 and median prior therapy lines was 2 (range, 1–6), with 107 pts (56%) receiving prior anti-PD1/PD-L1. 48 pts (25%) had BM at screening and 142 (74%) did not (No BM); data was missing for 2 pts (1%). Pts with BM were more likely to have received &gt; 3 prior lines of therapy (BM, 29%; No BM, 9%) and have a record of prior brain radiation (BM, 85%; No BM, 40%); otherwise, characteristics of pts with BM were generally similar to those without. Tarlatamab delivered comparable activity in pts with BM vs. those without in terms of objective response rate (ORR; 20%, 25%) and disease control rate (DCR; 59%, 50%) (Table). Median duration of response (DoR) was 14.9 months (BM) vs. 13.0 months (no BM). Median overall survival (OS) was 13.2 months in the BM group vs 15.5 months in the no BM group. Safety outcomes were similar in terms of treatment-related AEs (TRAEs; BM, 90%; No BM, 94%) and grade (gr) ≥ 3 (BM, 38%; No BM, 39%). Groups were also comparable with respect to immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events (any-grade, 6% vs 9%; gr ≥ 3, 4% vs 4%) and neutropenia (any-grade, 10% vs 15%; gr ≥ 3, 8% vs 8%). AEs numerically different in the BM vs No BM group included gr ≥ 4 TRAEs (17%, 7%) and any-grade CRS (67%, 54%). The only grade 5 TRAE (pneumonitis) occurred in the BM group. Conclusions: Tarlatamab continues to show promising efficacy and is generally safe in pts with ES SCLC irrespective of the presence of BM. Rates of ICANS and associated neurologic AEs were comparable between those with and without BM at baseline. Reference: 1. Paz-Ares L, et al. J Clin Oncol. DOI:10.1200/JCO.22.02823. Clinical trial information: NCT03319940 . [Table: see text]
Outcome of nasopharyngeal carcinoma (epithelial undifferentiated NOS) in children and adolescents: SEER database analysis.
Authors: Dinesh Pendharkar, Garima Nirmal, Adnan Ali, Neha Gupta
Journal: Journal of Clinical Oncology (2023)

e22016 Background: Nasopharyngeal carcinoma (NPC) is a rare malignant epithelial tumor of the nasopharynx and account for less than 1% of childhood tumors. Undifferentiated epithelial tumors are one of the commonest histologies. This study aimed to demonstrate the characteristics and outcome of NPC in children and adolescents. Methods: The Surveillance, Epidemiology and End Results database (SEER Research Data 18 Registries Nov 2020Sub (2000-2018)was analyzed for patients diagnosed with carcinoma undifferentiated NOS, NPC ( ICD-O-WHO-3 code 8020). Patients were excluded if the cause of death was not associated with their cancer according to SEER’s cancer-specific death categorization. Overall Survival were estimated using the Kaplan-Meier method, and variables were compared using the log-rank test. P values &lt; .05 were considered significant. Results: A total of 62 patients aged ≤19 years with undifferentiated nasopharyngeal carcinoma were identified. The cohort included 39 (62.9%) males and 23 (37.1%) females .Among them, 40.3 % were white, 40.3% were black,17.7% were Asians/Pacific Islanders, and 1.6% were American Indian. The age of diagnosis distribution included 2 (3.2%)children with 5-9 year, 17 (27.4%) children with 10-14 years and 43(69.4%) children with 15-19 years. With a median follow up of 7.9 years, 3 year OS of the entire cohort was 84.5%. 3 year OS for children aged ≤14 years was 82.1% and for children aged 15-19 years was 85.5% (p- value = 0.649). When stratified by treatment era, the 3-year OS of all patients treated after 2009 was not statistically significant than those treated before (3-year OS, 85.5% vs 82%, P = .0649). Conclusions: Children and adolescents with undifferentiated epithelial neoplasm NOS, NPC had excellent survival. Age and treatment era has no prognostic impact on outcomes.
Retreatment and rechallenge with BRAF/MEK inhibitors in patients with metastatic melanoma: Results from the observational study GEM1801.
Authors: Pablo Ayala de Miguel, Miguel-Angel Berciano-Guerrero, Eva Muñoz-Couselo, Jose Luis Manzano, Pablo CEREZUELA Fuentes, AINARA SORIA RIVAS, Almudena García Castaño, Guillermo Crespo, Teresa Puértolas, Carlos Aguado De La Rosa, Lourdes Gutiérrez Sanz, Rafael López Castro, Enrique Espinosa, Maria Jose Lecumberri, Margarita Majem, Javier Medina Martinez, Lorena Bellido, Luis Antonio Fernandez, Salvador Martin-Algarra, Ivan Marquez-Rodas
Journal: Journal of Clinical Oncology (2023)

9547 Background: Most patients with BRAF-mutant melanoma eventually develop resistance to therapy with BRAF/MEK inhibitors and immune-checkpoint blockade. Alternative treatment strategies are required in these patients since further therapy options lack survival benefit. Small series have shown promising activity from re-exposure to BRAF/MEK inhibitors after a treatment free interval of targeted therapy (TT), probably due to regression of resistant tumors and proliferation of clones that maintain sensitivity to BRAF/MEKi. However, prospective evidence for this approach is limited. Here we report the results of 30 patients who received a second course of TT at relapse after adjuvant therapy (retreatment) or after first progression on TT in the advanced setting (rechallenge). Methods: GEM1801 is a prospective observational study from the Spanish Melanoma Group (GEM) including 893 patients with melanoma treated in 37 centers. This is a descriptive analysis of basal characteristics, response rates (RR), progression free survival (PFS) and overall survival (OS) from 30 patients that received retreatment or rechallenge with BRAF/MEKi in GEM1801 study. Results: 4 patients received retreatment and 26 rechallenge. For retreatment, BRAF/MEKi median free interval from end of adjuvant TT to subsequent retreatment was 17.8 months (range: 12.4 - 57.7). RR with retreatment were 25%, with a median PFS and OS of 5.7 and 8.5 months. For rechallenge, RR was 38.5% and median PFS and OS 11.1 and 22.2 months respectively. Patients who were selected for rechallenge had higher complete response (CR) rates to first TT (26.9% vs 20.3%; p= 0.026). Patients who experimented deeper responses with 1st TT in the metastatic setting showed a correlation to longer PFS to 2nd TT with 12-m PFS rates of 66.7% versus 35.7% (HR 9.09 [95%CI: 1.42-58]; p= 0.02). OS showed a not statistically significant improvement in patients who reported CR to first TD (24-m OS rate of 75% versus 40.7% respectively). BRAF/MEKi free interval since first progression and retreatment or rechallenge was not associated with prognosis. Prognostic factors as LDH and number of metastatic sites did not correlate with the efficacy of retreatment. Conclusions: Retreatment or rechallenge with BRAF/MEKi in the metastatic setting achieved encouraging efficacy and may be a valid therapeutic strategy in a selected group of patients. Response to first treatment, retreatment and rechallenge with BRAF/MEKi. Clinical trial information: NCT03605771 . [Table: see text]
Real-world comparison between 6 weeks versus 3 weeks adjuvant pembrolizumab in high-risk stage IIB-IIID cutaneous malignant melanoma: Experience from an academic cancer center.
Authors: Manan Shah, Saba Shafi, Kari Lynn Kendra, Claire F. Verschraegen, Richard Cheng Han Wu
Journal: Journal of Clinical Oncology (2023)

9545 Background: The KEYNOTE-555 trial demonstrated similar efficacy and safety profile of 6-week (q6w) pembrolizumab (400 mg/m 2 ) vs 3-week (q3w) in unresectable and metastatic melanoma leading to FDA’s approval of this dosing schedule for adults in 2020. Limited real-world data is available on the use of 3 weeks vs 6 weeks pembrolizumab in the adjuvant setting in cutaneous melanomas. Q6w is hypothesized to cause more adverse effects due to higher drug concentration. Methods: We conducted a retrospective study of surgically resected Stage IIB-IIID cutaneous melanomas receiving adjuvant pembrolizumab from 2019-2022 at The James Comprehensive Cancer Center with a follow-up of ~1 year. Fifty patients [n=35 (q6w) and n=15 (q3w)] were included. The primary objectives were to compare disease free survival (DFS) and safety profile based on the NCI-CTCAE (v 5.0) criteria. Kaplan-Meier curves were generated for DFS comparisons between the two groups. Fisher’s exact test was used to compare the safety profile between the two groups. Accuracy of the sample size for final analysis was planned based on log rank test. With 15 patients (q3w) and 35 patients (q6w), our study had 80% power to detect differences in clinical outcomes. A p-value of less &lt; 0.05 was considered statistically significant. The secondary objective was to compare overall survival (OS) which will be reported later with a longer follow-up. Results: The mean age in the q6w and q3w groups was 59 years and 69 years, respectively. The median follow up was ~ 9 months with males predominating in both groups (54% and 18%). In the q6w group, 68% had ECOG status 0 (vs.30% in q3w) and most of our patients (32%) were stage IIIB (vs. 6% in q3w) and 28% were stage IIIC (vs 12% in q3wk). BRAF mutation was present in 32% in q6w vs. 2% in q3w. Toxicity profile was noted to be similar in both groups with no significant statistical difference ( p-value=0.4), though there were more Grade-3 immune-related toxicities in 7 patients in the q6w group (vs 3 in q3wk). The most common grade 3 toxicity noted was colitis (n=4, q6w; n=1, q3w). Notably, no significant difference was noted in the DFS between the two groups ( p-value=0.6). At the time of analysis, 3/15 (20%) patients in q3w and 7/35 (20%) in the q6w group had disease progression with the most common site being the regional lymph-nodes. At the time of the last follow up, 96% of the patients were alive with only 2 deaths occurring due to non-cancer related causes. Conclusions: We demonstrate comparable efficacy of q6w and q3w adjuvant pembrolizumab for advanced stage melanoma, with a trend towards increased immune-mediated colitis events in q6w. [Table: see text]
Genomic determinants of outcome in acute lymphoblastic leukemia: A Children’s Oncology Group study.
Authors: Ti-Cheng Chang, Wenan Chen, Abdelrahman Elsayed, Stanley B. Pounds, Mary Shago, Karen R. Rabin, Elizabeth A. Raetz, Meenakshi Devidas, Cheng Cheng, Anne L. Angiolillo, Andrew J. Carroll, Nyla A Heerema, Ilaria Iacobucci, Kelly W. Maloney, Ching-Hon Pui, Nilsa C. Ramirez, Stephen Hunger, Gang Wu, Charles Grenfell Mullighan, Mignon L. Loh
Journal: Journal of Clinical Oncology (2023)

10015 Background: While cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 90%, half of relapses arise in those originally classified with standard risk (SR) disease. Methods: We performed genome/transcriptome sequencing of diagnostic and germline samples of children with SR (n=1381) B-ALL or high-risk (HR) B-ALL with favorable cytogenetics ( ETV6: RUNX1 or double trisomy (DT) of chromosomes (chr) 4+10; n=115) to identify predictors of relapse. We used a case-control study to analyze 439 patients who relapsed and 1057 who remained in complete remission for &gt; 5 years. Results: Genomic subtype was associated with relapse. Unbalanced ETV6:RUNX1 translocations were more common than balanced in relapse patients (OR=2.01, CI=1.25-3.20, P=0.002). Conversely, balanced TCF3:PBX1 translocations were more often associated with relapse than unbalanced in TCF3:PBX1 ALL (OR=0.11, CI=0.01-0.50, P=0.003). A striking finding was the high relapse rate in PAX5 altered ALL (57 of 116 cases (49%); OR=3.29, CI=2.16-5.01, P=3.49x10 -8 ). The nature of the heterogeneous PAX5 driver alterations of this subtype influenced relapse risk, with internal PAX5 amplifications and biallelic PAX5 alterations associated with the highest risk. Specific chr gains influenced outcome in hyperdiploid ALL, with gain of chr 10 and disomy of chr 7 associated with favorable outcome (OR=0.27, CI=0.17-0.42, P=8.02x10 -10 , St Jude Children’s Research Hospital (SJCRH) validation cohort: OR=0.22, CI=0.05-0.80, P=0.009), while disomy of chr 10 and 17 and gain of chr 6 were enriched in patients that relapsed (OR=7.16, CI=2.63-21.51, P=2.19x10 -5 ; SJCRH cohort: OR=21.32, CI=3.62-119.30, P=0.0004). Genomic alterations were also associated with relapse in a subtype-dependent manner, including alterations of INO80 in ETV6:RUNX1, IKZF1 and CREBBP in hyperdiploid, and FHIT in Ph-like ALL. Conclusions: Genetic subtype, aneuploidy patterns, and secondary genomic alterations influence risk of relapse in children otherwise classified with SR ALL, or HR ALL with favorable genetics. Comprehensive genomic analysis is required for optimal risk stratification and treatment allocation, and particularly to study reduction of therapy in the lowest risk patients. [Table: see text]
Ethnic disparities in biomarker testing and targeted therapy use in metastatic lung adenocarcinoma: A 2014-2021 analysis.
Authors: Alyssa Pereslete, Ahmad Ozair, Atulya Aman Khosla, Shreyas S Bellur, Charlie Hurmiz, Suresh Marada, Andrea McCracken, Mark Layton Watson, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2023)

e21216 Background: Racial and ethnic disparities have been demonstrated to be widespread in lung cancer, including in the US. Despite insurance coverage for standard biomarker testing, testing rates remain low in minority populations. This work sought to analyze institutional data to assess whether there existed ethnic disparities in biomarker testing rates and receipt of targeted therapy between Hispanic/Latino and non-Hispanic/Latino patients of metastatic lung adenocarcinoma (mAdenoCa). Methods: A retrospective study was conducted and reported following ‘strengthening the reporting of observational studies in epidemiology’ (STROBE) guidelines. All Hispanic white and non-Hispanic white patients of mAdenoCa seen at our tertiary care institution in South Florida from 01/2014 to 12/2021 were identified and included through Guardian Research Network (GRN) platform. Socio-demographic, clinicopathological, and tumor molecular features along with treatment-related characteristics were analyzed via descriptive and comparative statistics. Results: A total of 268 mAdenoCa patients were included, of which 179 patients were Hispanic or Latino and 89 were not Hispanic or Latino. Biomarker testing data is reported in the table. Data of MET, KRASG12C, VKIRAS, and HER3 was not available in all cases. The unadjusted product-limit survival analysis indicated worse outcomes for Hispanic whites as compared to non-Hispanic counterparts. There were no differences found regarding targeted therapy use in either population. Conclusions: While metastatic lung adenocarcinoma patients at our center showed no differences in biomarker testing or targeted therapy use, the non-availability of data regarding several key mutations indicates a major dearth of testing. Future studies need to evaluate actionable strategies for improving the existing low testing rates in patients with mAdenoCa, particularly in racial and ethnic minorities. [Table: see text]